This research project is directed towards the synthesis and evaluation of B12-analogues as potential antitumor agents. Analogues of the coenzyme form of B12, methyl-B12 and 5'-deoxyadenosyl-B12 are being chemically synthesized. As part of this evaluation program, the uptake of the analogues by intact tumor cells will be studied. The B12-binding protein in ascitic fluid will be isolated, purified and characterized, and its role in the uptake of these B12-analogues by various tumor cells determined. Another aspect of the evaluation will be to determine the kinetics of inhibition of the B12-dependent enzymes, N5-methyltetrahydrofolate homocysteine methyltransferase and B12 reductase. Finally, the effect of these analogues on the in vivo growth of various tumor cells will be studied.